Michela Figorilli

Comparison between Automatic and Visual Scorings of REM Sleep without Atonia for the Diagnosis of REM Sleep Behavior Disorder in Parkinson Disease

Study Objectives: To compare three different methods, two visual and one automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD) in Parkinsons disease (PD) patients. Methods: Sixty‐two consecutive patients with idiopathic PD underwent video‐polysomnographic recording and showed more than 5 minutes of REM sleep. The electromyogram during REM sleep was analyzed by means of two visual methods (Montréal and SINBAR) and one automatic analysis (REM Atonia Index or RAI). RBD was diagnosed according to standard criteria and a series of diagnostic accuracy measures were calculated for each method, as well as the agreement between them. Results: RBD was diagnosed in 59.7% of patients. The accuracy (85.5%), receiver operating characteristic (ROC) area (0.833) and Cohens K coefficient (0.688) obtained with RAI were similar to those of the visual parameters. Visual tonic parameters, alone or in combination with phasic activity, showed high values of accuracy (93.5‐95.2%), ROC area (0.92‐0.94), and Cohens K (0.862‐0.933). Similarly, the agreement between the two visual methods was very high, and the agreement between each visual methods and RAI was substantial. Visual phasic measures alone performed worse than all the other measures. Conclusion: The diagnostic accuracy of RSWA obtained with both visual and automatic methods was high and there was a general agreement between methods. RAI may be used as the first line method to detect RSWA in the diagnosis of RBD in PD, together with the visual inspection of video‐recorded behaviors, while the visual analysis of RSWA might be used in doubtful cases.

Time structure of leg movement activity during sleep in untreated Parkinson disease and effects of dopaminergic treatment

OBJECTIVES To evaluate the specific time structure of periodic leg movements during sleep (PLMS) in untreated Parkinson disease (PD) patients by means of an advanced analysis; and to evaluate the effects of treatment on this activity, in a cross-sectional comparison and in a prospective follow-up study, in a subgroup of previously untreated patients. METHODS Forty-four consecutive PD patients were enrolled in the study; 19 had not yet started any drug therapy for PD (PDnother); 10 out of these patients were re-evaluated after an average time lag of 19.6months from baseline. The remaining 25 patients (PDther) were taking l-dopa and/or dopamine agonists. Eighteen age-matched normal controls were also included. All subjects underwent a polysomnographic recording and the time structure of their sleep leg movement activity was analyzed by means of the periodicity index and other advanced measures. RESULTS Both PD groups tended to show increased PLMS and decreased isolated limb movement activity with respect to controls. PLMS index >15/h was found in 26.3% of PDnother patients, 24.0% of PDther subjects, and in 16.7% of controls; none of the three PDnother patients who had PLMS index >15/h at baseline sustained this level at follow-up, nor did the other seven patients. The intermovement interval distribution showed a clear peak at 10-40s in the PDnother group; a suppression of this peak was observed after the introduction of dopaminergic treatment in the subgroup of 10 PDnother patients. Both groups of PD patients showed a progressively decreasing number of PLMS through the night; an almost complete abolition of PLMS was seen in the first 2h of sleep after the introduction of dopaminergic drug therapy. CONCLUSION Our data do not seem to support the hypothesis that PLMS are particularly frequent in PD but seem to indicate an interaction between PD pathophysiology and genetic predisposition for PLMS, producing a slightly increased number of patients with this sleep motor phenomenon when compared to controls.

Sleep and REM sleep behaviour disorder in Parkinson’s disease with impulse control disorder

Introduction Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson’s disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs. Methods Eighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case–control study. Forty patients (22 men; mean age: 62.6±9.7 years, Hoehn & Yahr: 2.1±0.6) with one or more current ICDs were age-matched and sex-matched with 40 patients with no history of ICDs (22 men, mean age: 64.9±7.8 years, Hoehn & Yahr: 2.2±0.6). They underwent a detailed sleep interview followed by a full-night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis included a clinical complaint of enacted dreams and/or documented behaviour during rapid eye movement (REM) sleep, with the presence of quantified REM sleep without atonia (RSWA). Results Patients with ICDs had a higher arousal index and higher RSWA than those without ICDs (51.9%±28.2%vs 32.2±27.1%, p=0.004). In addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was still associated with ICDs in a multivariate regression analysis including age of onset, PD duration and severity, treatment duration, levodopa-equivalent and dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI 1.3 to 18.5), p=0.02). Conclusions This large, controlled series of patients with PD with ICDs assessed by v-PSG confirms the association between ICDs and RBD. Increased surveillance of symptoms of ICDs should be recommended in patients with PD with RBD.

The Clinical Importance of Periodic Leg Movements in Sleep

Opinion statementPeriodic leg movements during sleep (PLMS) are commonly found in patients with restless leg syndrome (RLS), but they may occur in other sleep disorders and several medical conditions. Their prevalence increases with age, but they can also be observed in children. During the last decades, very active research has been devoted to determine and understand the pathophysiology, associated events, and clinical significance of PLMS. This chapter tries to sum up the most relevant PLMS-related findings, focusing on the relationship between PLMS and the cardiovascular system, in order to understand the clinical implication of this complex motor phenomenon. PLMS have been associated with sympathetic overactivity, namely surges in nocturnal blood pressure and heart rate, without modification in global autonomic balance. Also, PLMS have been related to inflammatory cellular pathways, with elevated level of inflammatory markers, which are associated with cardiovascular risk. The PLMS-related modulation of the autonomic system and of inflammation may increase cardiovascular and cerebrovascular risk in subjects with frequent PLMS. Moreover, also, comorbidities associated with PLMS may play a synergic role in worsening the cardiovascular risk and the consequent mortality and morbidity. Furthermore, little is known about pathophysiological correlates in children with PLMS and their chronic implication on the cardiovascular and cerebrovascular systems. A few studies have suggested that treating PLMS with dopaminergic drugs may reduce their associated sympathetic overactivity and modify disease progression. Definitely, further research is needed to assess the clinical impact of PLMS, associated or not with RLS, and above all the long-term impact of treating PLMS on cardiovascular risk, morbidity, and mortality.

Diffusion tensor imaging tractography and MRI perfusion in post traumatic brain injury hypersomnia

Three years ago, a 48-year-old female patient had head trauma with commotion followed by a four-month coma. After hospital discharge, she complained of bilateral frontal headache, amnesia related to the episode and excessive daytime sleepiness with prolonged non-restorative naps at any time of day. Previous patient history did not report neurological or psychiatric illness. At our first outpatient sleep service (besides a normal neurological exam), she did report severe sleep disturbances, particularly an incoercible daytime sleepiness followed by non-refreshing and prolonged naps (Epworth Scale 18), prolonged night-time sleep with snoring and a noteworthy morning sleep inertia. Multiple repeated night videopolysomnography (PSG) excluded limb movements and respiratory disturbances and no REM behavior disorder was evident (preserved regular REMmuscle atonia). Nocturnal PSG showed four complete cycles [sleep latency 4.5 min, TST 6 h and 40 min, sleep efficiency 91% with normal NREM\REM alternationwhile increased N3 rate (N14%, N2 33%, N3% 41, REM 22%)]. Next-daymultiple sleep latency test (MSLT) showed a pathological mean sleep latency of 5.1 min without evidence of SOREMPs (mean REM-latency

F-Wave Duration as a Specific and Sensitive Tool for the Diagnosis of Restless Legs Syndrome/Willis-Ekbom Disease

STUDY OBJECTIVES Restless legs syndrome, also known as Willis-Ekbom disease (RLS/WED), is a frequent condition, though its pathophysiology is not completely understood. The diagnosis of RLS/WED relies on clinical criteria, and the only instrumental tool, the suggested immobilization test, may lead to equivocal results. Recently, neurophysiological parameters related to F-wave duration have been proposed as a diagnostic aid. The aim of this study is to assess and compare the diagnostic values of these parameters in diagnosis of RLS/WED. METHODS Fifteen women affected by primary RLS/WED and 17 age- and sex- matched healthy subjects. A complete electroneurographic evaluation, including nerve conduction studies (NCS), cutaneous silent period (CSP), and F-wave parameters, namely amplitude, F-wave duration (FWD), and the ratio between FWD and duration of the corresponding compound muscle action potential (FWD/CMAPD). RESULTS No subject showed alterations of the NCS. However, FWD and FWD/CMAPD of both upper and lower limbs were significantly longer in patients than controls. Tibial FWD/CMAPD best discriminated RLS/WED patients from controls. A cutoff of 2.06 yielded a sensitivity of 69.2%, a specificity of 94.1%, a positive predictive power of 90%, and a negative predictive power of 80% (area under the curve = 0.817; 95% confidence interval = 0.674-0.959). The combination of ulnar or tibial FWD/CMAPD increases the sensitivity (85.7%) while slightly decreasing the specificity (87.5%, positive predictive value: 85.7%, negative predictive value: 87.5%). CONCLUSIONS Lower limb FWD/CMAPD ratio may represent a supportive diagnostic tool, especially in cases of evening lower leg discomfort of unclear interpretation.

Restless Legs Syndrome/Willis–Ekbom Disease and Periodic Limb Movements in Sleep in the Elderly with and without Dementia

There is great interest in the study of sleep in healthy and cognitively impaired elderly. Sleep disorders have been related to quality of aging. Sleep-related movements are a frequent cause of disordered sleep and daytime sleepiness. Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is often unrecognized in the elderly. This review explores RLS/WED in the elderly population. The elderly population may be subdivided into 3 groups: healthy, dependent, and frail. The RLS/WED could be a predictor for lower physical function; its burden on quality of life and health care-related costs, in the elderly, should be an important clinical and public health concern.

Periodic Leg Movements During Sleep and Cardiovascular and/or Cerebrovascular Morbidity

Purpose of ReviewTo evaluate if periodic leg movements during sleep (PLMS) may be associated with increased cardiovascular or cerebrovascular morbidityRecent FindingsPLMS are accompanied by rises in hear rate and blood pressure and by important transient EEG changes indicating sleep fragmentation; in addition, PLMS have been related to elevated levels of inflammatory markers that are associated with increased cardiovascular and cerebrovascular risk and several reports have suggested that PLMS may play an important role in increasing cardiovascular risk, resulting in hypertension, cardiac ischemic disease, and cerebrovascular disease.SummaryAlthough a body of evidence suggests that PLMS are involved in increasing cardiovascular risk, additional studies are needed to establish the contributory role of PLMS to cardiovascular homeostasis and morbidity in patients with and without RLS, and to evaluate the role of the specific PLMS treatment to reduce the risk.

Sleep in Parkinson’s Disease with Impulse Control Disorder

Purpose of ReviewThis paper aims to explore the relationship between impulse-control disorders (ICDs) and sleep problems in patients with Parkinson’s disease (PD) among scientific literature.Recent FindingsPreviously published results are controversial and sometimes inconclusive. ICDs and sleep disruption represent important non-motor features of Parkinson’s disease, responsible for reducing quality of life and increasing burden of disease. The relationship between sleep problems and ICDs is complex and bidirectional. Indeed, sleep disturbances and fragmentation may play a crucial role in increasing susceptibility to impulsive behavior and may represent a risk factor for developing ICDs in PD patients. Moreover, REM sleep behavior disorder (RBD) and restless legs syndrome (RLS) have been indicated as independent risk factors for ICDs in PD patients. On the other hand, also ICDs may lead to sleep restriction and fragmentation, suggesting a bidirectional relationship.SummaryThe association between sleep problems and ICDs in PD is far from being completely understood. Further studies are needed to confirm the nature of this relationship and its pathophysiology.

Rapid eye movement atonia is not rapid eye movement sleep behavior disorder

We have read with interest the paper by Bolitho et al. recently published in Movement Disorders, assessing the ability of four screening questionnaires to correctly identify rapid eye movement (REM) sleep without atonia (RSWA) in patients with Parkinson disease (PD). We also agree with Dr. Postuma’s editorial about the importance of comparing different screening tools “head to head.” However, we believe that the validity of the study results might be significantly limited by some problematic aspects. RSWA is a crucial feature of REM sleep behavior disorder (RBD); however, it only represents one of the diagnostic criteria, and its exact extent has not yet been defined, especially in patients with RBD and PD. Nevertheless, authors implicitly assume equivalence between RSWA and RBD, and surprisingly enough, do not provide any data about the diagnosis of RBD according to standard criteria (eg, International Classification of Sleep Disorders, 2nd edition at the time of the study). Given these premises, measures of sensitivity and specificity of the different screening questionnaires could not be obtained. But even assuming “equivalence” between RSWA and RBD, the study found an unexpectedly high rate of falsepositive RBD diagnosed by questionnaire (eg, subjects who scored positively on the questionnaire but did not have RSWA), and a virtual absence of false-negative (subjects who are unaware of their RBD but who exhibit RWSA). This is very surprising, in light of studies showing that 18% of PD patients without a history of dream-enacting behaviors actually have RSWA or video-behavioral RBD manifestations or reporting a sensitivity of only 33% for the clinical interview for RBD in PD patients. According to our and others’ experience, detection of RSWA in unaware PD patients, especially those without a bed partner, is not uncommon. This raises some concerns about the methodology used to assess sleep in these patients. First, Bolitho et al. do not mention how they scored REM sleep stage in this population (eg, allowing the presence of muscle tone during REM sleep in all subjects). Second, but even more critical, they provide no data about video-recorded behaviors during nocturnal polysomnography, which are an essential part of the diagnostic criteria according to the ICSD-2. Actually, the authors stated that sleep was assessed with ambulatory polysomnography without mention of concomitant video-recording. If this is true, the calculation of RSWA appears to be at least problematic. Indeed, authors need to explain how they could correctly assess REM sleep epochs in RBD patients, and especially how they differentiated EMG changes related to RBD episodes from those attributable to normal arousals during REM sleep, body position changes, cough, wakefulness, and so forth. To what extent was EMG activity related to RBD episodes included or excluded from their calculation of RSWA? Conversely, if video-recording was performed and carefully inspected, the authors should give details of RBD episodes observed in questionnaire-positive and -negative RBD patients. In conclusion, we believe that the mere comparison of results of two sets of parameters (questionnaires and RSWA), both of which are not perfect indicators of a disorder (RBD), cannot be performed without a clear and sound clinical diagnosis of the disorder itself, following established standard criteria. The evident lack of information and the probable impossibility of establishing such a firm diagnosis (with the data available in the paper) make these results not conclusive.